The invention relates to a sensor- and/or separating element comprising a membrane arrangement which can be used in particular for the separation of substances and for the detection of molecules in sensor elements as part of separating devices for chemical substances or as part of electrochemical measuring cells and can be used preferentially for chemical analysis in biotechnology and industrial process control.
The invention further relates to a process for the production of the aforesaid sensor- and/or separating element and the use thereof.
As part of an electrochemical measuring cell for the separation of gas molecules and detection in a three-electrode system, DE 3 841 621 C2 has disclosed polymer membranes arranged on support bodies with channels of 50-300 xcexcm length disposed at a distance from the edge of 5 xcexcm, said polymer membranes conventionally being polymer membranes used for semi-permeable oxygen diffusion. They are characterised by the fact that the support body consists of metals or plastics with a conductive surface coating. This design is also characterised by an electrolyte which is arranged in the channel structures and together with the metallized or conductive surface forms the three-phase boundary vis-a-vis electrolytic gas.
Similar arrangements comprising a metallic support body as electrode are described in U.S. Pat. No. 3,767,552.
Another device comprising support bodies of the previously mentioned type which form capillaries or capillary-like openings is described in DE 4 018 597 and U.S. Pat. No. 5,202,011. These known arrangements are characterised by solid support structures with relatively long channels between a polymer covering layer and further elements of electrochemical measuring cells. As such solid, voluminous support bodies have a poor molecule-separating capacity, no applications have previously been described for these.
Additionally, DE 41 15 414 C2 has disclosed a sensor- and/or separating element for the semi-permeable diffusion of molecules comprising a mechanically stable substrate having a a through-opening and the semi-permeable membrane arranged in the through-opening. This publication has also disclosed a process for the production of a separating- and/or sensor element wherein a through-opening is formed in a substrate by a processing means, a semi-permeable membrane is introduced into the through-opening and a plurality of electric terminals connected to the membrane are formed.
As here the semi-permeable membrane is formed in the through-openings in that a liquid is introduced therein, from which liquid an ion-selective membrane then forms, relatively thick membranes are obtained which substantially fill the depth of the through-openings very limited. The diffusion capacity is consequently very limited. To improve the diffusion capacity it is necessary to reduce the thickness of the substrate and the cross-sectional area of the through-openings. The possible extent of such a reduction is however dependent upon the particular materials used and therefore such a reduction is possible only to a very limited extent since the stability and durability of the semi-permeable layer and the overall structure are impaired by such a reduction.
Finally, WO 91/11710 A1 has disclosed a sensor- and/or separating element for the semi-permeable diffusion of molecules comprising a mechanically stable substrate having a through-opening and a perforated, semi-permeable membrane connected to the substrate. This document also discloses a process for the production of a sensor- and/or separating element wherein a through-opening is formed in the substrate by a processing means, a semi-permeable membrane is applied to the substrate in such manner that the through-opening is spanned and a plurality of electric terminals are formed.
As in this known sensor- and/or separating element the semi-permeable membrane spans the through-openings, the membrane must be relatively thick if it is to span the relatively large-area through-openings in a stable manner or the cross-sectional area of the through-openings must be relatively small if the membrane is to be made relatively thin. In either case a mutual dependency exists between the nature of the membrane material, the cross-sectional area of the through-openings and the minimum thickness of the membranes with which adequate stability and durability of the membrane across the through-openings are provided. In practice, as in the case of the above described sensor- and/or separating element according to DE 41 15 414 C2, these conditions lead to a relatively low diffusion throughput with relatively limited stability and fairly limited durability of the semipermeable layer.
The object of the present invention is in particular to provide a sensor- and/or separating element of the type mentioned in the introduction which, while providing excellent mechanical stability and durability of the semi-permeable layer, permits a substantially increased diffusion of the molecules to be detected and/or separated.
This object is achieved in accordance with the invention by a sensor and/or separating element for the semi-permeable diffusion of molecules comprising the following:
a) a mechanically stable substrate having at least one through-opening,
b) a perforated membrane which is fluid tightly connected to the substrate and which extends at least across the through-openings; and
c) at least one semi-permeable layer which is applied in firmly adhering manner to one or both sides of the membrane at least in the perforated region thereof in that the semi-permeable layer or semi-permeable layers is/are secured mechanically in the adjacent perforations and/or by chemical-structural and/or physical adhesion and/or adhesive intermediate layers and/or covalent surface bonding to the adjacent surfaces of the membrane, optionally of the substrate or a metallic film optionally additionally applied to one or both sides of the membrane.
In this way the invention provides a sensor- and/or separating element which permits the throughputs of molecules to be varied and adjusted as desired by means of a practically arbitrary selection of the size and spacing of the perforations of the membrane to which the semi-permeable layer is applied.
Such a sensor- and/or separating element facilitates the provision of a membrane which serves as support membrane for the semi-permeable layer or layers and which is an ultra-thin membrane whose thickness preferably ranges between 50 xcexcm and 10 nm, particularly preferably between 20 xcexcm and 100 nm.
Preferably, depending upon its embodiment, the sensor- and/or separating element according to the invention is designed in such manner that
A) the semi-permeable layer preferably is a polymer layer, more perferably it consists of one or more organic polymers which is/are preferably adherent or adhesive-like and/or
B) the substrate and the membrane are made of similar or different materials from the group consisting of mechanically stable, inorganic and organic materials; and/or
C) the substrate and the membrane are made of similar or different organic polymers; and/or
D) the organic polymers are from the group consisting of polycarbonate, polystyrene, polytetrafluoroethylene and polyamide; and/or
E) the material of the membrane differs from the material of the substrate in respect of its processibility by a predetermined chemical and/or physical processing means, such that the substrate can be removed by the processing means whereas the membrane substantially cannot be attacked by the processing means; and/or
F) the membrane preferably consists of silicon, one or more silicon compounds and/or a material containing silicon and/or another semiconductor material, and particularly preferably the membrane consists of silicon dioxide, silicon nitride, silicon oxynitride, glass and/or quartz, while the substrate consists of a material which can be chemically converted into the membrane material or can be coated with the membrane material in firmly adhering manner; and/or
G) the perforations have a diameter or maximum diameter which ranges between 0.1 and 50 xcexcm, preferably 1 and 10 xcexcm; and/or
H) the optional metallic film extends over a region of the substrate or a region of the membrane underlaid by the substrate; and/or
I) a metallic film or a plurality of metallic films is/are provided, which consist(s) of individual segments which are separate from one another and each of which is provided with at least one electric terminal; and/or
J) a further metallic film or one or more further double layers of metallic film plus semi-permeable layer are applied to the exterior of one or both semi-permeable layer(s), optionally a final metallic film being applied to the outermost semi-permeable layer and all the further metallic films being perforated in the region of the through-opening(s); and/or
K) the membrane is electrically non-conductive or semiconducting and the metallic film on one or both side(s) of the membrane(s) and/or on one or more semi-permeable layer(s) consists of individual segments separate from one another, each of which is provided with at least one electric terminal.
A particularly preferred substrate-membrane material combination is that in which both materials are semiconductor materials, preferably silicon-based materials, such as for example silicon as substrate material and epi-silicon as membrane material.
Another particularly perferred substrate-membrane material combination is that in which both materials are organic polymers, either similar or different organic polymers, e.g., chosen from the group consisting of polycarbonate, polystyrene, polyethylene, polytetrafluoroethylene, polyamide and/or other organic polymers. Such organic polymers can be perforated e.g. by laser radiation, laser ablation, ion beams, preferably followed by etching, or e.g. by mechanical machining as e.g. drilling, milling, embossing, stamping or the like. Such membrane and substrate made of organic polymer can preferably be a thin and a thick foil laminated or adhered together to form the substrate-membrane combination.
In this way, in accordance with the invention, an arrangement comprising one or more semi-permeable layers having the function of molecule-separating membranes, a support element formed as membrane (support membrane) and optionally one or more sensorial metallic films is improved upon in such manner that the support function is now assumed by a mechanically stable membrane integral with the substrate and preferably consisting of inorganic constituents and the semi-permeable layer is connected thereto in firmly adhering manner, thereby facilitating a diffusion improved to a high level with a reduced depth dimension. The metallic film forms a metallic, sensor-like element as used as sensorial component of electrochemical measuring cells and is optionally applied to the interior and/or exterior of the membrane.
In accordance with the invention, in place of the previously conventional voluminous lattice-, capillary or sieve/filter constructions, a preferably ultra-thin mechanical membrane is used. Here it is possible to use a technological process as conventionally employed in silicon technology and micromechanics with which, for example by the etching of silicon, glass or the like, pits, holes or the like can be produced as through-openings in silicon, glass and other materials, where at the end of such a through-opening an ultra-thin layer of membrane-forming organic materials, such as silicon dioxide, silicon nitride, silicon oxynitride or epi-silicon remains as membrane and thus the material of said membrane is selected such that it is not attacked by the etching agent or the like of the substrate. The thickness of such membranes is determined and adjusted by the preceding application of the materials to the substrate, which consists for example of silicon, glass or the like.
For example by means of a photolithographic process using wet-chemical or dry-etching procedures it is possible to introduce pores and openings of any desired size as perforations into the membrane so that an adjustable permeability is achieved via the size and number of these openings.
These perforations and their permeability are of particular advantage for adjusting the diffusion or penetration of molecules or atoms through the supporting membrane.
For the provision of a sensorial element, such as an electrode, or in order to change the chemical surface structure, preferably ultra-thin metallic films are applied, for example in accordance with the known technological principle of sputtering or thermal vapour deposition, to the upper side or rear side of the support membrane onto the pit-like through-openings. These metallic films can be provided externally or internally with an electric connection line to enable them to be used for example as electro-chemically operating electrodes. Due to the preferably planar arrangement, the metallic films can be structured in a simple manner, for example by mask technology, and then used as multi-channel electrodes.
The mechanical structuring of the membrane, which supports the semi-permeable layer(s), with perforations has a particularly advantageous effect in that these serve as mechanical fixing means for the semi-permeable layer(s), perferably produced from plastics material, which is/are optionally applied to one or both sides of the membrane. To strengthen the adhesion, known surface modifications can be provided, such as silanisation or chemical bonding with bifunctional reagents following the functionalisation of the surface.
The arrangement of semi-permeable layers, such as polymer membranes, on ultra-thin support membranes has the advantage that these can be designed for high diffusion rates of molecules, such as for example those af gases, and for this reason they can also fulfil separating functions, for example in gases.
The metallic films can be used as an electrochemical sensor element in cooperation with the semi-permeable layers, such as for example polymer membranes, and used for example as electrodes in electrochemical cells, it being possible to use conventional electrolytes and additional electrodes on one side of the sensor- and/or separating element.
The invention also provides a process for the production of the sensor- and/or separating element according to the invention which is in no way limited to the particularly preferred embodiments of specific process steps referred to in the foregoing only by way of example, but rather generally comprises the following detailed process steps:
(a) providing a mechanically stable substrate;
(b) forming at least one through-opening in the substrate;
(c) fluid-tightly connecting a membrane to the substrate such that the membrane extends at least across the through-opening;
(d) forming perforations through the membrane in the region of the through-opening(s);
(e) applying at least one semi-permeable layer in firmly adhering manner to one or both sides of the membrane at least in the region thereof spanning the through-opening(s), preferably also to the adjacent region of the substrate, in that the semipermeable layer or semi-permeable layers is/are secured mechanically in the adjacent perforations and/or by chemical-structural and/or physical adhesion and/or adhesive intermediate layers and/or covalent surface bonding to the adjacent surfaces of the membrane and optionally of the substrate.
This process can preferably be realized in detail by:
(1) applying a metallic film on one or both sides of the membrane and forming one or more electrical terminals connected to or formed by the membrane(s); and/or
(2) with the substrate and the membrane being made of similar or different materials from the group consisting of mechanically stable, inorganic and organic materials; and/or
(3) the substrate and the membrane being made of similar or different organic polymers;
(4) prefably in the latter case the organic polymers being from the group consisting of polycarbonate, polystyrene, polytetrafluoroethylene and polyamide.
Another process provided by the invention comprises the following detailed process steps:
a) provision of an electrically insulating or semiconducting membrane on a mechanically stable substrate such that the membrane is integral with the substrate, where the material of the membrane differs from the material of the substrate in respect of its processibility by a predetermined chemical and/or physical processing means, such that the substrate can be removed by this processing means whereas the membrane substantially cannot be attacked by the same processing means;
b) formation of at least one through-opening in the substrate by the processing means so that the through-opening is closed off on one side by the membrane;
c) formation of perforations in the region of the membrane extending across the through-opening;
d) application of at least one semi-permeable layer in firmly adhering manner to one or both sides of the membrane at least in the region thereof spanning the through-opening(s), preferably also to the adjacent region of the substrate in that the semi-permeable layer or semi-permeable layers is/are secured mechanically in the adjacent perforations and/or by chemical-structural and/or physical adhesion and/or adhesive intermediate layers and/or covalent surface bonding to the adjacent surfaces of the membrane and optionally of the substrate or of a metallic film optionally additionally applied to one or both sides of the membrane.
If, as is possible within the scope of the invention, an electrically conductive membrane is used instead of an electrically insulating or semiconducting membrane, the process according to the invention can also be executed in the above manner, it being possible to use the electrically conductive membrane as metallic film which can be provided with one or more electrically conductive terminals.
In accordance with a further development of the above processes according to the invenion, sensor- and/or separating elements of elaborate structures can be produced in that a further metallic film or one or more double layers of metallic film plus semi-permeable membrane(s) are applied to the exterior of one or both semi-permeable layers, where optionally a final metallic film is applied to the outermost semi-permeable membrane and where all the further metallic films are perforated in the region of the through-opening(s) and where the further metallic film or one or more or all of the further metallic films can be formed in the segmented manner described in the following.
Preferred embodiments of the above process according to the invention are additionally characterised in that:
1) a metallic film or a plurality of metallic films is/are produced from segments separate from one another, each segment preferably being provided with or electrically conductively connected to at least one separate terminal and/or
2) the perforations are formed with a diameter or maximum diameter ranging between 0.1 and 50 xcexcm, preferably 1 and 10 xcexcm and/or
3) the semi-permeable layer(s) is/are applied by a spin-off process, centrifugal or fluidized-bed coating, or spin-or jet coating and/or
4) mechanical machining, laser ablation, chemical wet etching, plasma dry-etching, electro-erosion or thermal melting-out is used as means of forming the through-opening(s) and/or
5) all or a part of the perforations are formed by photolithography in association with dry- or wet etching or by laser beam processing or by ion beam processing and/or
6) the metallic film or all the metallic films or a part of the metallic films is/are applied by sputtering, vapour deposition, plating, electrolytic deposition or current-free electrolytic deposition.
Further preferred features of the invention are described in the claims.
The sensor- and/or separating element according to the invention and/or produced by the process according to the invention can be used in particular for the detection of electro-chemically active molecules and for the separation of molecules through the semi-permeable layer(s).
The advantage of the invention consists in particular in that the preferably ultra-thin membrane results in improved material transport properties and improved fixing of the semi-permeable layer(s), for example in the form of polymer membranes, on the supporting membrane. A further advantage consists in the preferably very cheap production using conventional semiconductor technology or plastics technology processes and in the very easily variable arrangement and dimensioning of the perforations in the membrane (support membrane). Compared with the previously conventionally used processes in LIGA technology or bulk micro-machining with voluminous support elements, exceptional advantages are obtained in terms of economy and handling.